It is known that endogenous (age-related) or exogenous (light-induced) aging leads to an irreversible degeneration of tissues, in particular of skin. These modifications result from a reduction of anabolic reactions (syntheses) and an increase of catabolic reactions (degradation) of collagen and elastin, the two main constituents of the skin matrix.
The synthesis reactions in the skin matrix are mostly regulated by polypeptides, so-called growth factors and cytokines. Among these peptides, TGFβ1 is one of the most important regulators involved in the synthesis reactions of this skin matrix. It is secreted in the matrix by keratinocytes and fibroblasts in a latent form and has to be activated in order to be recognized by the cell receptors and to be able to induce a biological response (collagen and elastin synthesis). Two forms of latent TGFβ1 are available:                a small, latent complex composed of 2 TGFβ-chains that are non-covalently bound to a so-called “latency associated protein” (LAP).        a large, latent TGFβ1-complex, in which the small, latent TGFβ1-complex is covalently bound (disulfide bonds) by the LAP to another, so-called “latent TGFβ binding protein” (LTBP). It has been found recently that in human skin this large, latent TGFβ1-complex is associated to fibrillin, a microfibril-forming molecule; these microfibrils are themselves bound to elastin. Thus, the large, latent TGFβ1-complex constitutes the greatest reservoir of latent TGFβ1 in skin.        
There are several physiological mechanisms to activate TGFβ1. The main method in vivo is the activation of latent TGFβ1 by thrombospondin-1 (TSP-1), a protein secreted by the skin cells. This activation bases on the interaction between the LAP of the latent TGFβ1 and the tripeptide sequence RFK (Arg-Phe-Lys) of TSP-1, XFX (with X=basic amino acid) being the smallest sequence required for the activation of latent TGFβ1.
During the aging process the bioavailability and the TGFβ1 activity are reduced by a decreased genetic expression and a modified capacity of fixing to fibroblast receptors. These modifications cause weakened synthesis reactions of the elastin and collagen fibres. The degradation reactions in the skin matrix are mainly produced by proteolytic enzymes, the matrix proteinases (MMPs).
MMP-1 (or collagenase) and MMP-2 (or gelatinase A) secreted by skin fibroblasts are involved in the chrono-induced aging process. Their number increases in aging skin, leading to a modification of collagen and elastin fibres. In the photo-induced aging process the MMP-9 (or gelatinase B) and MMP-3 (leukocyte elastase) are involved. They are secreted by keratinocytes and/or polynuclear neutrophils during UV-induced, inflammatory processes, whereby the elastin and collagen fibres are degraded and reduced (elastose).
Consequently, the decreased anabolism and the increased catabolism of the macromolecules in the skin matrix lead to an imbalance that is responsible for the appearing of the following clinical symptoms: skin atrophy, loss of the mechanical properties with relief and elasticity loss, skin flabbiness, deep mimic wrinkles, accelerated formation of wrinkles and streaks, and disappearance of the natural skin lines.
In order to prevent the above mentioned modifications and clinical symptoms, and to improve the appearance of the skin surface in particular by reducing the wrinkle depth and eliminating fine wrinkles, it would be sensible to apply substances capable of simultaneously exerting the following effects:                activation of the synthesis reactions in the skin matrix by stimulating the growth factor (TGFβ1) activity responsible for the anabolism of the macromolecules of the extracellular matrix        reduction of the degradation reactions in the skin matrix by modulating the metalloproteinase activity responsible for the catabolism of the macromolecules in the extracellular matrix and protection of these components from the influence of these enzymes.        
As collagen represents about 80% of the skin proteins, it is easily understandable that the smallest diminution of its tissue concentration may have considerable consequences for the mechanical and physiological properties of skin.
It has been surprisingly found that it is possible to synthesize cosmetically active tripeptides and derivatives thereof (hereinafter referred to as “compounds of the present invention”) and topically applicable, cosmetic compositions against chrono- and photo-induced skin aging (anti-aging products), which may diffuse rapidly and in sufficient concentration through the cell membrane up to the intracellular site of action and produce a rapid and strong stimulation of collagen synthesis. This results from the capacity of the compounds of the present invention to activate the synthesis reactions in the skin matrix by specifically stimulating the growth factor TGFβ1 responsible for the anabolism of macromolecules in the skin matrix.
Therefore, the compounds of the present invention exert a stimulating effect on the extracellular matrix, which decisively influences the mechanical and physiological appearance of skin.
It could be shown that replacing the central amino acid in the tripeptide sequence RFK (Arg-Phe-Lys) of TSP-1 by an amino acid bearing an alkyl chain optionally substituted by hydroxy as a side chain, together with substituting the peptide with a penetration-enhancing, lipophilic group result in a quicker diffusion through the cell membrane up to the intracellular site of action in higher concentration and that the compounds of the present invention thus produce a quicker and stronger stimulation of collagen synthesis than the compound elaidyl-Lys-Phe-Lys corresponding to the state-of-the-art and described in the patent application FR 2810323 published on 21 Dec. 2001.